Interleukin-6 and the granulocyte colony-stimulating factor receptor are major independent regulators of granulopoiesis in vivo but are not required for lineage commitment or terminal differentiation

Fulu Liu, Jennifer Poursine-Laurent, Huai Yang Wu, Daniel C. Link

Research output: Contribution to journalArticlepeer-review

113 Scopus citations

Abstract

Multiple hematopoietic cytokines can stimulate granulopoiesis; however, their relative importance in vivo and mechanisms of action remain unclear. We recently reported that granulocyte colony-stimulating factor receptor (GCSFR)-deficient mice have a severe quantitative defect in granulopoiesis despite which phenotypically normal neutrophils were still detected. These results confirmed a role for the G-CSFR as a major regulator of granulopoiesis in vivo, but also indicated that G-CSFR independent mechanisms of granulopoiesis must exist. To explore the role of interleukin-6 (IL-6) in granulopoiesis, we generated IL-6 x G-CSFR doubly deficient mice. The additional loss of IL-6 significantly worsened the neutropenia present in young adult G-CSFR-deficient mice; moreover, exogenous IL-6 stimulated granulopoiesis in vivo in the absence of G-CSFR signals. Near normal numbers of myeloid progenitors were detected in the bone marrow of IL-6 x G-CSFR- deficient mice and their ability to terminally differentiate into mature neutrophils was observed. These results indicate that IL-6 is an independent regulator of granulopoiesis in vivo and show that neither GCSFR or IL-6 signals are required for the commitment of multipotential progenitors to the myeloid lineage or for their terminal differentiation.

Original languageEnglish
Pages (from-to)2583-2590
Number of pages8
JournalBlood
Volume90
Issue number7
StatePublished - Oct 1 1997

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